Certain medical tests have become highly automated. For example common tests such as measuring a patient's cholesterol levels or blood sugar, testing for the presence of drugs in a subject's blood or urine, or measuring other aspects of a patient's blood chemistry can now be performed by automated testing machines at rates up to thousands of tests per hour. In a typical test, a sample such as a quantity of a patient's blood is reacted with a reagent, and the resulting product studied to determine the presence or amount of a particular analyte in the sample. The reagent may be specifically designed for the performance of the particular test.
Because important medical decisions may be made on the basis of the test results, it is highly desirable that the testing machines be qualified periodically to maintain confidence that the machines are operating properly, or to try to detect when the machines are not operating properly. In fact, U.S. government regulations require such periodic validation. By regulation, each testing machine must be qualified at least once per day for any day that patient testing is performed.
Qualification may involve testing a sample having known characteristics, and checking whether the machine produces a test result that agrees with the known characteristics. If so, the machine may be assumed to be operating properly, and if not, the operation of the machine may be suspect.
Machine qualification thus requires the ready availability of test samples having known characteristics. These test samples used for machine qualification may be called “quality control materials”. Because a single testing machine may be able to perform a large number of different tests, including testing for an analyte using different reagents, and because testing machines from different manufacturers may perform tests differently, the number of quality control materials that must be readily available is very large, in order to qualify every kind of machine in the performance of every test it is capable of. For at least some tests, for example tests that test for unusual conditions in human tissue or unstable analytes, it may be impracticable to maintain a reserve of actual biological samples having known characteristics, so the quality control material may mimic the behavior of an actual biological sample. Quality control materials are preferably stabilized, so that they can be stored for long periods. For example, some quality control materials are lyophilized at the time of manufacture, and reconstituted for use.
Because of natural variability in the process of manufacturing quality control materials, each new lot of a particular quality control material is characterized at the time of its manufacture, to determine a range of test result values within which a result from a test of a sample from the lot is expected, with a specified probability, to fall when the quality control material is tested using a testing instrument that is operating properly. A mean value is also typically published. These means and ranges, known as assay means and ranges, are published for the use of testing laboratories in the qualification of their machines. Means and ranges may be published for each possible combination of testing machine model and quality control material, or testing method and quality control material.
Recent guidance from the U.S. Food and Drug Administration requires that published assay means and ranges for quality control materials be statistically valid.